CA2101845A1

CA2101845A1 - Composition and use of substituted 1,3-dithiolo- and 1,4-dithiinoquinoxalines as an antimicrobial

Info

Publication number: CA2101845A1
Application number: CA002101845A
Authority: CA
Inventors: Duane R. Romer; R. Garth Pews; Ravi B. Shankar
Original assignee: Individual
Current assignee: Dow Chemical Co
Priority date: 1991-12-30
Filing date: 1992-12-04
Publication date: 1993-07-01
Also published as: US5200409A; EP0784083A3; DE573635T1; WO1993013106A1; DE69226171D1; DE69226171T2; EP0784083A2; EP0573635A1; EP0573635B1

Abstract

Substituted 1,3-dithiolo- and 1,4-dithiinoquinoxalines are prepared which correspond to formula (I), wherein X represents (A) or (B) and R1 and Rindependently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group. These compounds have been found to exhibit antimicrobial and marine antifouling activity in industrial and commercial applications and compositions containing these compounds are so employed.

Description

WO 93/13106 Pcl/US92/lo476 21018~

1,3-DITHIOLO-AND 1,4-DITHIINOQUINOXALINES
ASAN ANTIMICROBIAL

The fi el d of this i nvention is novel substituted quinoxaline compounds which are useful as antimicrobiai and marine antifouiing agents.
Saikachi,H.andTagami,S.,YakugaukuZusshi,82, 1246-51 (1962),disclosesthe preparation of a compound of the formula:
N S ~CN

~N S CN

which is used as an intermediary in the preparation of a compound of the formula:

[~X ~N~

~:. 20 : :~q-US-A-3761475 discloses the preparation of a compound of the formula~

,X~ X 5 3/\CN

which is usefui as a fungicide and bactericide~ .

~ ~ . . ..
~, -1 - ' ' ' :, `

~, .. ".,, . ,, , . .... . .. ., . , ., ~

WO 93/13106 21~18 l15 PCI'/US92/10476 JP-A-01215069 discloses a compound of the formula ~ C R 3 wherein R3 and R4 may be cyano and R1 and R2 may form a substituted heterocyclic aromatic ring. This compound is useful in a photoactive layer in a photoelectric conversion element.
JP-66/013397 discloses a compound of the formula:

~ N ~ S 3~CN

which is useful in a fungicidal composition.
Foye, W. 0. et al., Journal of Pharmaceutical Sciences, Vol. 64, No. 2, ~5 February 1975, pp. 211-216, "SynthesisandAntimalarial Activityof HeterocyclicAlkyl Disulfides, Thiosulfates, and Dithio Acid Derivatives", disclosesthe preparation of a compound of the formula:

N X 5 >= \
which ;s screened for antimalarial activity.
The desirability of identifying or discovering new antimicrobial and/or marine 25 antifoulant agents is widely recognized. New agents are desired for several reasons; these include, but are not limited to, rffponding to the problem created by the development of ~ .
microbe strains resistantto known agents, the occurrence of undesirable interactions of certain known agents with the medium or product in which the agent is used, and high toxiclty of certain known agents to certain non-target organisms such as mammals.
The present invention solves these problems by disclosing new compounds which may be employed as an antimicrobial and/or a marine antifoulant agent.
Thepresentinventionisacompoundcorrespondingtotheformula:

X Formula I ~ :

'.

.

, .: , , :r ,~ . . : ` : : :: .

WO 93/13106 PCr/US92/10476 ~ 2101~
wherein X represents:
CN
CN \ C
\C=C or / \CN / \CN
and R1 and R2 independently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, wherein the alkyl, alkoxy, arylcarbonyl, or alkoxy carboxyl may be with or without halogen substituents, provided that at least one of Rl and R2 is -`
10 a nitro, cyano, alkoxy, arylcarbonyl, or an alkoxy carbonyl group. ~.
The present invention is also an antimicrobial composition comprislng an inert diluent and an antimicrobially-effective amount of the cornpounds corresponding to Formula 1.
The present invention is also a method for inhibiting microorganisms in a microbial habitat comprising contacting said microbial habitat with an 15 antimicrobially-effective amount of the compounds corresponding Formula to 1.The present invention is also the use of the compounds corresponding to Formula I as a microorganism inh;bitor.
The present invention is also a composition useful in preventing the growth of :
marine organisms on a surface exposed to a marine environment in which marine organisms 20 grow comprising an inert diluent and a marine antifouling effective amount of the compounds corresponding to Formula 1. . : ;.
The present invention is also a method for preventing the growth of marine organisms on a surface exposed toa marine environment in which marine organisms grow ;~ comprising contacting said surface with a marine antifouling effective amount of a cornpound ~-25 correspondingtotheformula:
S~X

:.: 30 wherein X represents:
: ~ CN :::
" \ / : : .
CN `C
~; C=C or . / \CN / \CN
.

~ 3 ~ ' WO 93/13106 2 1 û 1~ PCI /US92/10476 and R1 and R2 independently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, wherein the alkyl, alkoxy, arylcarbonyl, or alkoxy carbonyl may be with or without halogen substituents.
~ he present invention is also the use of a compound corresponding to the 5 formula:
~X N ~ S

wherein X represents: .
CN . :.
/CN \ C ~ :, 15/C=C \ or C
CN / \CN ..

and R1 and R2 independently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, wherein the alkyl, alkoxy, arylcarbonyl, or alkoxy ~ .
20 carbonyl may be with or without substituents, as a marine organism ;nhibitor.The 1 ,3-dithiolo- and 1 ,Withiinoquinoxaline compounds of the prffent . .
invent;on correspond tothe formula:

~5 ~5/ ~ ~

wherein X represents~
CN
/CN \ C
C=C or C
\CN / \CN ~ -;

and Rl and R2 independently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, wherein the alkyl, alkoxy, arylcarbonyl, or alkoxy carbonyl may be with or without substituents. Typical Iy, it is preferred that at least one of R1 : .
and RZ is a nitro, cyano, alkoxy, arylcarbonyl, or an alkoxy carbonyl group. In one embodiment W093/13tO6 2101 ~ PCI/US92/10476 of the present invention, it is preferred that R1 and R2 are not both halogen. Preferably, R1 represents CN, CO2CH3, OCH3, COC6H5, or No2 when R2 represents H or Rl represents H, Cl, CH3 or NO2 when R2 represents NO2. Most preferably, one or both of R1 and R2 represents NO2.
In the present specification and claims, the term " halogen" is employed to 5 designate fluorine, chlorine, bromine, iodine, or astatine. Preferably, halogen i5 employed to designate fluorine, chlorine, bromine, or iodine.
In the present specification and clai ms, the term "alkyl ~ is employed to designate straight chain and branched chain alkyls. Such alkyls may be with or without substituents, such as halogen. Preferably, the term Nalkyl" is employed to designate straight chain alkyls of 1 to 6 -10 carbon atoms and branched chain alkyls of 3 to 6 carbon atoms. Most preferably, the term "alkyl" isemployedtodesignatestraightchainalkylsof 1to4carbonatoms,suchasmethyl,ethyl, propyl or butyl and branched chain alkyls of 3 to 4 carbon atoms, such as isopropyl or : .
tertiary butyl. : . .
In the present specification and claims, the term nalkoxy~ is employed to 15 designate a group of the formula: .

wherein R3 represents an alkyl group, which may be with or without substituents, such as halogen. Preferably,thetermNalkoxy~isemployedtodesignateanalkoxywithanalkylgroup. of l to 6 carbon atoms. Most preferably, the term ~alkoxy~ is employed to designate an alkoxy 20 with an alkyl group of 1 to 3 carbon atoms, such as methoxy or ethoxy. :
In the present specification and claims, the terrn ~arylcarbonyl ~ is employed to designate a group of the formula:
O :' ~ 25 wherein R4 represents an aryl group, which may be with or without substituents, such as halogen.
In the present specification and claims, the term N aryl ~ is employed to designate : . .
- groups which have the ring structure characteristic of benzene, wherein the ri ng may be with or without substituents such as alkyl, cyclic alkyl, alkoxy, or hatogen. The aryl ring may also be a .i 30 fused ring, wherein the ring may have one or more of its sides i n common with another ring.
Preferably, the aryl ring has no more than three substituents. Most preferably, the aryl is ,~ phenyl.
In the present specification and claims, the term " alkoxy carbonyiN is employed to designate a group of the formula:

-C-ORs , . . .
wherein Rs represents an alkyl group, which may be with or wlthout substituents, such as haloge . Pleferably, the term Nalkoxy carbonyl N is employed to designate an alkoxy carbonyl 5- , .

WO 93/13106 2 1 0 ~ 8 4 5 PCl/US92/10476 ;
with an alkyi group of l to 6 carbon atoms. Most preferably, the term " alkoxy carbonyl " is : .
employed to designate an alkoxy carbonyl with an alkyl group of 1 to 3 carbon atoms, such as ` -methyl carboxy ester or ethyl carboxy ester.
Compounds of the present invention wherein X represents CN
C :.
.. . .
/C\ ~ , CN
10 may be prepared by the reaction of an appropriately substituted 2,3-dichloro-6-quinoxaline precursor with disodi~Jm dimercaptomaleonitri)e. The general reaction schome for this -reaction is as follows: . .

1S~ N C1 NaS XCN R~ N S ~N : ~ :~
R N C l NaS CN R N S
.
.
The use of disodium dimercaptomaleonitrile to prepare other compounds is known and and is 20 generallydisclosed in US-A-376147S; US-A-4172133; U~A-4199581 and U~A-4210645.
As used herein, the term ~appropriately substituted 2,3-dichloro-6-quinoKaline precursor~ is meant to refer to a compound of the formula: . :
R ~ N XCl ~: 25 R~ N Cl wherein Rl and R2 independently represent the hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group necessary to achieve the desired substituted 1,3-dithiolo- or 1,4-dithiinoquinoxaline final product.
. Compo~nds of the present i nvention wherein X represents:
CN
- \C=C\ ` "'''' / CN ~.. .. :

WO ~3/13106 PCI/US92/10476 ` ` ' 2 ~
. .
may be prepared by the reaction of an appropriately substituted 2,3-dichloro-6-quinoxaline precursor with di(sodiomercapto)methylenemalononitrile or di(potasio-mercapto)methylenemalononitrile. The general reaction scheme forthis reactian is as follows:
R ~ N Cl NaS~:N ~ S ~CN

R~ N XC1 NaS CN 2~ N S CN

The use of di(sodiomercapto)methylenemalononitrile to prepare other compounds is known ~ -l O and is generally disclosed in US-A-4038393; US-A-4075204 and US-A-4075205 In carryi ng out these reactions, the appropriatel y substituted 2,3-dichloro-6-quinoxaline precursor and the di(sodiomercapto) or :
di(potassiomercapto)methylenemalononitrile and/or disodium dimercaptomaleonitrile are typically mixed together in substantially equimolar amounts. The reactions, however, are 15 generallynotlimitedtotheuseofthesodiumsaltofthedimercaptans ~ypically,anysuitabie alkaline or alkali earth metal salt may be used such as, for example, the dipotassium salts of the dimercaptans.
The reactions are typically carried out at room temperature under an ambient prffsure of an inert gas in the presence of a polar, aprodc solvent, such as dimethylformamide 20 or dimethylsulfoxide. Typically, any order of addition of the reagents may be used and the reagents may be added neat or as a solut;on in the solvent used for the reaction. Subsequent ~ I
to the addition of the appropr;ate reaction reagents, the reaction mixture will typically be allowed to continue at a temperature of between 25C to 60C over a period of 1 to 24 hours. ~ ;~
The reaction product maytypically be isolated by adding a 3 to lO vdume excess of water 25 which will precipitate the desired product. Filtration followed by washing and drying yields the desired 1,3-dithiolo- and/or 1,4-dithiinoquinoxaline compounds of the present invention.
Svnthesisof IntermediateAoDroDriatelvSubstituted 2 3-Dichloro-~Quinoxaline Thesynthesisoftheappropriatelysubstituted2,3-dichloro-~quinoxaline precursor beginswith the chlorination of an appropriately substituted 30 2,3-dihydroxyquinoxaline. This chlorination is straightforward and is described in the art, such as in Cheeseman, G.W.H., J. Chem. Soc.,1962, p.1170.
The following examples illustrate the present invention and the manner by which it can be practiced but, as such, should not be construed as limitations upon the overall scope of the same.

~ ' ' '.
:: . 7 .

` : `

:.,. ; ~ . . , . " '': .' " .',. ', ~ ' . ' :

WO 93/13tO6 PCI/US92/10476 2iO~45 Pre~ar_tion of 1,4-Dithiinc~(2,3-b)quinoxalines-2,3-Dicarbonitriles Example 1 Pre~aration of 7-Nitrs~-1.4dithiino(2,3-b~uinoxaline-2.3-dicarbonitrile To a solution of 2,3-dichloro-6-nitroquinoxaline (1.0 9,0.0041 mol) in dimethylformamide (20 mL) is added, in several portions, disodium-5 -Z-1,2^dicyano-1,2-ethylenedithiolate(1.1 g,O.0045mol). Theresultingsolutionisstirred overnightatroomtemperature. Water(lOOmL)isslowlyaddedtothereactionmixture, dropwise, with stirring. The resulting solid is isolated by filtration, washed with water and dried, giving a dark purple powder.
The recovered material weighs 0.92 9 and has a melting po;nt of 222 to 225C. A10 calculated overall yield of 72 percent isachieved.
The structure identity is confirmed by proton nu~lear magnetic resonance spectroscopy (1 H), carbon nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR) and mass spectrometry (MS).
Example2 Pre~arationof7,8 Dinitr~1,4-dithiino-(2,3-b)quinoxaline-2,3-dicarbonitrile The process of Example 1 is followed except that the 2,3-dichloro--~nitroquinoxaline is replaced by 1.25 9 of 2,3-dichloro-6,7-dinitroquinoxaline and 0.966 9 of the disodium-Z-1,2-dicyano-1,2-ethylenedithiolate is used. The recovered material is a reddish powderweighing 1.16gwithacalculatedoverallyieldof75percentandhasameltingpointof 230 to 233C.
Example 3 PreDaration of 7-Chloro-1.4dithiino-~2.3-b)auinoxaline-2,3-dica~bonitrile The process of Example 1 is followed except that the 2,3-dichloro--6-nitroquinoxaline is replaced by 3.00 9 of 2,3,~trichloroquinoxaline and 2.99 9 of the disodium-Z-1,2-dicyano-1,2-ethylenedithiolate is used. The recovered material is a dark orange powder weighing 2.87 9 w;th a calculated overall yield of 74 percent and has a melting point of 278 to 280C.
Example 4 Preparation of 7-Methvl-1.4-dithiino-(2,3-b)auinoxaline-2,3-dicarbonitrile r The process of Exam ple 1 is fol lowed except that the 2,3-dichl oro--6-nitroquinoxaline is replaced by 3.0 9 of 2,3-dichloro-6-methylquinoxaline and 3.3 9 of the disodium-Z-1,2-dicyano-1,2-ethylenedithiolate is used. The recovered material is an o-ange powder weighing 3.52 9 with a calculated overall yield of 88 percent and has a melting point of 213to215C
Example 5 Pre~aration of 1,4-Dithiino-(2.3-b)-quinoxaline-2,3-dicarbonitrile The process of Example l is followed except that the 2,3-dichloro--6-nitroquinoxaline is replaced by 4.0 9 of 2,3-dichloroquinoxaline and 4.68 9 of the disodium-Z-1,2-dicyano-1,2-ethylenedithio!ate is used. The recovered material is a reddish powder weighing 4.58 9 with a calculated overall yield of 85 percerit and has a melting point of greater than 300C.

.; . : - , - ..

-` 2101~$
Example 6 Preparation of 7-Nitro-8-methyl-1,4-Dithiino-~2,3-b)-quinoxaline-2.3-dicarbonitrile The process of Example 1 is followed except that the 2,3-dichloro--6-nitroquinoxaline is replaced by l .5 9 of 2,3-dichloro-6-nitro-7-methylquinoxaline and 1.4 9 .
of the disodium-Z- 1,2-dicyano- l ,2-ethylenedithiolate is used. The recovered material is a dark :
orange powder weighing 1.5 9 with a calculated ov~erall yield of 79 percent and has a melting - ~.
point of 155 to 157C.
Example 7 Pre~aration of 7-Chlor~8-nitrc~1.4-dithiino-(2.3-b)-cluinoxaline-2,3-dicarbonitrile ` The process of Example 1 is followed except that the 2,3-dichloro-10 -6-nitroquinoxaline is replaced by 1.0 9 of 2,3-dichloro-6-chloro-7-nitroquinoxaline and 0.81 9 ~ -of the disodium-Z-1,2-dicyano-1,2-ethylenedithiolate is used. The recovered material is an orange powder weighing ~.9û 9 with a calculated overatl yield of 72 percent and has a melting .
pointof228to230C. .: ~.
Example 8 Pre~aration of 7-Cvano-1,4-di_hiino-(2,3-bi-auinoxaline-2.3-dicarbonitrile TheprocessofExamplelisfollowedexceptthatthe2,3-dichloro--6-nitroquinoxaline is replaced by û.33 9 of 2,3-dichloro-6-cyanoquinoxaline and 0.39 9 of the - : :.
disodium-Z- 1,2-dicyano- 1,2-ethylenedithiolate is used. The recovered material is a yellow powder weighing û.34 9 with a calculated overall yield of 79 percent and has a melting point of 218 to 220C.
20 Example 9 Preparation of 7-Carbomethoxy-1,4dithiino-(2,3-b)-quinoxaline--2,3-dicarbonitrile The process of Example 1 is followed except that the 2,3-dichloro--6-nitroquinoxaline is replaced by 0.5S g of 2,3-dichloro-~carbomethoxyquinoxaline and 0.56 9 ofthedisodium-Z-1,2-dicyano-1,2-.ethylenedithiolateisused. Therecoveredmaterialisadark 25 orange powder weighing 0.36 9 with a calculated overall yield of 53 percent and has a melting point of 133 to 135C.
Example 10 Prer aration of 7-Methoxv- 1,4-dithiino-~2.3-b)-auinoxaline-2,3-dicarbonitrile : ~ ~ The process of Example 1 is followed except that the 2,3-dichloro--6-nitroquinoxaline i5 replaced by 0.75 9 of 2,3-dichloro-6-methoxyquinoxaline and 0.76 9 of 30 the disodium-Z-1,2-dicyano-1,2-ethylenedithiolate is used. The recovered material is a dark orange powder weighing 0.81 9 with a calculated overall yield of 82 percent and has a melting : point of 154 to 156C.
Example 11 Preparation of 7-Trifluoromethyl-1,4-dithiino-(2,3-b)-quinoxaline--2.3-dicarbonitrile The process of Example 1 is followed except that the 2,3-dichloro- ..
-6-nitroquinoxaline is replaced by O.S0 9 of 2,3-dichloro-6-trifluoromethylquinoxaline and 0.49 9 of the disodium-Z-1,2-dicyano-1,2-ethylenedithiolate is used. The recovered material is ~ ,, .

21018 ~ ~ PCI`/US92/10476 an orange powder weighing 0.18 9 with a calculated overall yield of 29 percent and has a meltingpointof 197to 199C.
Example 30 Pre~ion of 7-Benzoyl- 1,4-dithiino-(2,3-b)-auinoxaline-2.3-d icarbonitri le The process of Example 1 is followed except that the 5 2,3-dichloro-6-nitroquinoxaline is replaced by 1.50 9 of 2,3-dichloro-6-benzoylquinoxaline and 1.0 9 of the disodium-Z-1,2-dicyano-1,2-ethylenedithiolate is used. The recove~ed material is a reddish-brown powder weighing 1.2 g vyith a calculated overall yield of 65 percent.
Preoaration of 1,3-Dithiolo-(4,5-b)-qu;noxaline-2-vlidene-Dropanedinitriles Example 12 Preparationof6-Nitro-1,3-Dithiolo-(4,5-b)-quinoxaline-2-ylidene-To a solution of 2,3-dichloro-6-nitro-quinoxaline (O.S g,0.002 mol) in dimethylformamide ~15 mL) isadded, in several portions, di(sodio-mercapto)methylenemalononitrile (0.53 9, O.Oû29 mol). The resulting soiution is stirred overnight at room ternperature. Water (50 mL) is slowly added to the reaction rnixture, dropwise, with stirring. The resulting solid is isolated by filtration, washed with water and dried, giving 0.48 9 (78 percent yield) of a dark brown powder.
Example 13 Pre~aration of 6-Nitro-1,3-dithiolo-t4.5-b)-quinoxaline-2-vlidene-~roDanedinitrile The process of Example 12 is followed except that the di(sod;omercapto)-20 methylenemalonon;trile is replaced ~y di(potassiomercapto)methylenemalononitrile (0.63 9, 0.0029 mole). The recovered material is a dark brown powder, weighing 0.48 9 w;th a r ~.
calculated overall yield of 78 percent and has a melting point of 220 to 222C.Example 14 Preparat;on of 6,7-D;n;tro-1,3~ith;olo-(4,~b)-qu;noxaline-2-yl;dene--DroDaned;nitrile The process of Example 13 is followed except that the 2,3-dichloro--6-nitroquinoxalineisreplacedbyl.25gof2,3-dichloro-6,7-dinitroquinoxalineand 1.13gof the di(potassiomercapto)methylenemalononitrile is used The recovered material is a dark brownpowderweighing1.26gwithacalculatedoverallyieldof82percentandhasamelting point greater than 300C.
30 ExamplelS Preparationof6-Methyl-1,3-dithiolo-(4,5-b)-quinoxaline-2-ylidene--oroDanedin;tr;le The process of Example 13 is followed except~that the 2,3-d;chloro--6-n;troquinoxal;ne ;s replaced by 3.0 9 of 2,3-dichloro-6-methylquinoxaline and 3.84 9 of the di(potass;omercapto)methylenemalonon;tr;le is used. The recovered material is a yellow 35 powder we;ghing 2.9 9 with a calculated overall yield of 73 percent and has a melting point of 265 to 267C.

-1 0- "

WO 93/13106 2 1 0 1 ~ ~ 5 PCT/US92/10476 Example 16 Preparation of 6-Chloro-1,3-dithiolo-(4,5-b)-quinoxaline-2 ylidene--propanedinitrile The process of Example 13 is followed except that the 2,3-dichloro-6-nitroquinoxaline is replaced by 3.0 9 of 2,3,6 trichloroquinoxaline 3nd 3.5 g of 5 the di(potassiomercapto)methylenemalononitrile is used. The recovered material is a dark brown powderweighing 3.0 9 with a calculated yield of 78 percent and has a melting point greater than 3ûOC.
Example 17 PreDarationof 1.3-Dithiolo-(4,5-b)-quinoxaline-2-vlidene-orooanedinitrile The process of Example 13 is followed except that the 2,3-dichloro-10 -6-nitroquinoxaline is replaced by 3.0 9 of 2,3-dichloroquinoxaline and 3.95 9 of the di(potassiomerca~oto)methylenemalononitrile is used. The recovered material is a light tan powder weighing 2.8 g with a calculated overall yield of 69 percent and has a melting point greater than 32ûC.
Example 18 Preparation of 6-Chloro-7-nitro-1,3-dithiolo-(4,5-b)-quinoxaline-2-ylidene-1 5 -~roDanedinitrile The process of Example 13 is followed except that the 2,3-dichloro--6-nitroquinoxaline is replaced by 1.5 9 of 2,3,6-trichloro-7-nitroquinoxaline and 1.4 9 of the di(potassiomercapto)methylenemalononitrile is used. The recovered material is a rust colored powder weighing 1.23 g with a calculated overall yield of 66 percent and has a melting point of 20 297 to 299C
Example 19 Preparation of ~Nitro-7-methyl-1,3-dithiolo-(4,5-b)-quinoxaline-2-ylidene--woDanedinitrile The procffs of Example 13 is followed except that the 2,3-dichlor~
-~nitroquinoxaline is replaced by 1.5 g of 2,3-dichloro-6-nitro-7-methylquinoxaline and 1.5 9 25 of the di(potassiomercapto)methylenemalononitrile is used. The récovered material is a dark .
yellow powder weighing 1.35 g with a calculated overall yield of 71 percent and has a melting point of 283 to 284C.
Example 20 Preparation of 6-Cyano-1,3-dithiolo-(4,5-b)-quinoxaline-2-ylidene- .. ~ .. .
-DroDanedinitrile :
The process of Example 13 is followed except that the 2,3-dichloro--6-nitroquinoxaline is replaced by 0.33 g of 2,3-dichloro-6-cyanoquinoxaline and 0.39 9 of the di(potassiomercapto)methylenemalononitrile is used. The recovered material is a yellow .. -powder weighing 0.33 9 with a calculated overall yield of 76 percent and has a melting poi nt of 278 to 281 C.

_......... ., . ,. , , ... , ... ., ~ .. ,, . ;.. . - ;

WO 93/13106 2 1 0 ~ 8 4 5 PCl'/US92/10476 Example 21 Preparation of ~Trifluoromethyl-1,3-dithiolo-(4,5-b)-quinoxaline-2-ylidene--oropanedinitrile The process of Example 13 is followed except that the 2,3-dichloro--6-nitroquinoxaline is replaced by 0.50 9 of 2,3-dichloro-6-trifluoromethylquinoxaline and 5 0.49 9 of the di(potassiomercapto)methylenemalononitrile is used. The recovered material is a dark yellow powder weighing 0.56 9 with a calculated overall yield of 88 percent and has a melting point of 197 to l 99C.
~xample 22 Preparation of ~Methoxy-1,3-dithiolo-(4,5-b)-quinoxaline-2-ylidene--oroDanedinitrile The process of Example 13 is followed except that the 2,3-dichloro--6-nitroquinoxaline is replaced by 0.75 9 of 2,3-dichloro-6-methoxyquinoxaline and 0.90 9 of the di(potassiornercapto)methylenemalononitrile is used. The recovered material is a dark yellow powder weighins 0.78 9 with a calculated overall yield of 79 percent.
Example 31 Preparation of 6-Benzoyl-1,3-dithiol~(4,5-b)-quinoxaline-2-ylidene--Drooanedinitrile The proces; of ~'xample 13 is followed except that the 2,3-dichloro--6-nitroquinoxaline is replaced by 1.5 9 of 2,3-dichloro-6-benzoylquinoxaline and 1.2 g of the di(potassiomercapto)methylenemalononitrile is used. The recovered material is a reddish brown powder weighing 1.0 9 with a calculated overall yield of 54 percent.
20 Antimicrobial Activitv The compounds of this invention are useful as antimicrobial additives to such industrial products as styrene-butadiene latexes used for paper coatings, paints, inks, adhesives, soaps, cutting oils, textiles, and piper and pigmentslurries. The compounds are also useful as antimicrobial additives in such personal care products as hand creams, lotions, 25 shampoos, and hand soaps. A further advantage of this invention is its cost-effectiveness for - applications which need to have an anti microbial conti nuously replenished, such as in cool ing i:~ ' towers and pulp and paper mills.
As appreciated in the art, not all of the compounds disclosed herein are active at - the same concentrations or against the same microbial species. That is, there is some ' 30 compound-to-compound variation in antimicrobial potency and spectrum of antimicrobial activity.
The present invention is also directed to a method for inhibiting microorganisms ~
which comprises contacting said microorganisms or habitat thereof with an effective amount of the compound of this invention.
The antimicrobial compounds of this invention may be added directly to aqueous formulations susceptible to microbial growth, either undiIuted or dissolved in inert diluents such as organic solvents such as glycols, alcohols, or acetone. They may also be'added alone or in combination with other preservatives.

W O 93/13106 PC~rtUS92/10476 21018~
As used herein, the term " microorganism ~ is meant to refer to bacteria, fungi,viruses, algae, subviral agents and protozoa.
As used herei n, the term " anti rnicrobially-effective amount" refers to that ~ :
amount of one or a mixture of two or more of the compounds, or of a composition comprising S such compound or compounds, of this invention needed to exhibit inhibition of selected microorganisms. Typically,thisamountvariesfromprov;ding 1 partpermill;on(ppm)to S,000 ppm by weight of the compound to a microbial habitat being contacted with the compound. Such amounts vary depending upon the particular compound tested and microorganism treated. Also, the exact concentration of the compoundsto be added in the 10 treatment of industrial and consumer formulations may vary within a product type depending upon the components of the formulation. A preferred effective amount of the compound is from 1 ppm to 500 ppm, more preferably from 1 ppm to 50 ppm by weight, of a microbial - habitat.
The term " microbial habitat" refers to a place or type of site where a microorganism naturally or normally lives or srows. Typically, such a microbial habitat will be an area that comprises a moisture, nutrient, and/or an oxygen source such as, for example a cool ing water tower or an air washing system.
The terms "inhibition~, ~inhibit~ or "inhibiting" refer to the suppression, stasis, kill, or any other interference vvith the normal life procffses of m;croorganisms that is adverse 20 to such microorganisms, so as todestroy or irreversibly inactivate existing microorganisms `
andJor prevent or control their future grovvth and reproduction.
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W O 93/13106 PCT/~S92/10476 TABLE I
_ .
No. Che~ical Identity A 7-nitro-1,4-dithiino-(2,3-b)-quinoxaline--2,3-dicarbonitrile : .
7,3-dinitro-1,4-dithiino-(2,3-b)-quinoxaline--2,3-dicarbonitrile - :
C 7-chloro-1,4-dithiino-(2,3-b)-quinoxaline--2,3-dicarbonitrile _ _ .
D 7-methyl-1,4-dithiino-(2,3-b)-quinoxaline--2,3-dicarbonitrile E 1,4-dithiino-(2,3-b)-quinoxaline- ~
-2,3-dicarbonitrile F 7-nitro-8-~ethyl-1,4-dithiino--(2,3-b)-quinoxaline-2,3-dicarbonitrile . ._ ._ G 7-chloro-a-nitro-1,4-dithiino--(2,3-b)-quinoxaline-2,3-dicarbonitrile H 7-cyano-1,4-dithiino-~2,3-b)-quinoxaline--2,3-dicarbonitrile I 7-carbomethoxy-1,4-dithiino-(2,3-b)-guinoxaline--2,3-dicarbonitrile 7-methoxy-1,4-dithiino-(2,3-b)-guinoxaline--2,3-dicarbonitrile . _ 7-trifluoro~ethyl-1,4-dithiino--(2,3-b)-guinoxaline-2,3-dicarbonitrile .
2S L 6-nitro-1,3-dithiolo-~4,5-b)-quinoxaline--2-ylidene-propanedinitrile . .~ . ; .
M 6,7-dinitro-1,3-dithiolo-(4,5-b)-quinoxaline--2-ylidene-propanedinitrile . :
N 6-~ethyl-1,3-dithiolo-(4,5-b)-quinoxaline-: ~ -2-ylidene-propanedinitrile :: 30 6-chloro-1,3-dithiolo-~4,S-b)-quinoxaline--2-ylidene-propanedinitrile . . . p 1,3-dithiolo-(4,5-b)-quinoxaline-2-ylidene-::~ . -propanedinitrile . .
Q 6-chloro-7-nitro-1,3-dithiolo--(4,5-b)-quinoxaline-2-ylidene-propanedinitrile 35 _ _ R 6-nitro-7-~ethyl-1,3-dithiolo--(4,5-b)-quinoxaline-2-ylidene-propanedinitrile :' .

~ -14-, : .- . ,: , , ., ~ :

W O 93/t3tO6 PCT/US92/tO476 21018~5 TABLE I

~6-cyano-1,3-dithiolo-(4,5-b)-quinoxaline-S -2-ylidene-propanedinitrile :.:
T 6-trifluoromethyl-1,3-dithiolo--(4,5-b)-quinoxaline-2-ylidene-propanedinitrile 6-methoxy-1,3-dithiolo-(4,5-b)-quinoxaline . -V 7-benzoyl-1,4-dithiino-(2,3-b)-quinoxaline--2,3-dicarbonitrile . :
W 6-benzoyl-1,3-dithiolo-(4,5-b)-quinoxaline--2-ylidene-propanedinitrile ' ' ' ` ' ',, , : 25 .

~ :.

.~ .
', ' "' ' WO 93/13106 2 1 ~ 1 ~ 4 ~ PCI/US92/10476 .. .,_, ~ ' The antimicrobial activity of the compounds of the present invention is demonstrated by the following techniques.
The mini mum inhibitory concentration (M IC) for the compounds listed in Table I is determined for 9 bacteria, using nutrient agar; and 7 yeast and fungi, using malt yeast agar. A
5 one percent solution of the test compound is prepared in a mixture of acetone and water.
Nutrient agar is prepared at pH 6.8, representing a neutral medium, and at pH 8.2, representing an alkaline medium. The nutrient agars are prepared by adding 23 9 of nutrient agar to one-liter of deionized water. In addition, the alkaline medium is prepared by adjusting a 0.04 M solution of N-ltris-(hydroxymethyl)methyl3-glycine buffered deionized water with - 10 concentratedsodiumhydroxidetoapHof~.5. Maltyeastagarispreparedbyadding3gyeast extract and 45 9 malt agar per liter of deioni~ed water. The specific agar is dispensed in 30 ml aliquots into 25 x 200 mm test tubes, capped and autoclaved for 15 minutes at 115C. The test tubescontainingtheagararecooledinawaterbathuntilthetemperatureoftheagaris48C.
Then, an appropriate amount of the one percent sol ution of the test compound is added (except in the controls where no compound is added) to the respective test tubes so that the final concentrationsare500,250,100,50,25,10,5,2.5,1.0andzeropartspermillionofthetest compound in the agar, thus having a known concentration of test compound dispersed therein. The contents of the test tubes are then transferred to respective petri plates. After drying for 24 hours, the petri plates containing nutrient agar are inoculated with bacteria and ~1 20 thosecontainingmaltyeastagarareinoculatedwithyeastandfungi.
The inoculation with bacteria is accomplished by using the following procedure.
Twenty-four hour-cultures of each of the bacteria are prepared by incubating the respective bacteria in tubes containing nutrient broth for 24 hours at 30C in a shaker. Dilutions of each of the 24 hour-cultures are made so that nine separate suspensions (one for each of the nine test 25 bacteria) are made, each containing 108 colony forming units (CFU) per ml of suspension of a particular bacteria. Aliquots of 0.3 ml of each of the bacterial suspensions are used to fill the individual wells of Steer's Replicator. For each microbial suspension, 0.3 ml was used to fill threewells(i.e.,threewellsofO.3mleach)sothatfortheninedifferentbacteria,27wellsare filled. The Steer's Replicator is then used to inoculate both the neutral and alkaline pH nutrient 30 agar petri plates~
The inoculated petri plates are incubated at 30C for 48 hours and then read to determineifthetestcompoundwhichisincorporatedintotheagarpreventedgrowthofthe respective bacteria.
The inoculation with the yeast and fungi is accomplished as follows. Cultures of35 yeast and fungi are incubated for seven days on malt yeast agar at 30C. These cultures are used to prepare suspensions by the hllowing procedure. A suspension of each organism is preparedbyadding10mlofsterilesalineand 10microlitersofoctylphenoxypolyethoxy ethanol to the agar slant of yeast or fungi. The sterile saline/octylphenoxy polyethoxy ethanol ~ 16-, WO93~13106 . ~ 4!~ P~US92/10476 solution is then agitated with a sterile swab to suspend the microorganism grown on the slant.
Each resulting suspension is diluted into sterile saline (1 part suspension: 9 parts sterile saline).
Aliquots of these dilutions are placed in individual wells of Steer's Replicator and petri plates inoculated as previ ~usly described. The petri plates are~ incubated at 3ûC and read after :
5 48 hours for yeast and 72 hours for fungi.
Table ll lists the bacteria, yeast and fungi used in the MIC test described above along with their respective American Type Culture Collection (ATCC) ide~ntification numbers.
TABLE II
Organisms used in the Minimum Inhibitory Concentration Test : . .
Organism ATCC No. :
~acteria .
Bacillus subtilis (Bs) 8473 Enterobacter aerogenes (Ea) 13048 : 15 Escherichia coli (Ec) 11229 Klebsiella pneumoniae (Kp) ô308 .. :
Proteus vulgaris (Pv) ~ ~ 881 P_eudomonas aeruginosa (Pa) 10145 : 20 P_eudomonas aeruginosa (PRD-10) 15442 Salmonella cholerae_ui-q (Sc) 10708 _ ., Staphylococcus aureus (Sa) 6538 : ~eas.t/Fungi : . Aspergillus niger (An) 16404 Candida albicans (Ca) l10231 : Penicillium chrysogenum (Pc)9480 . .:
. ~ ., Saccharomyces cerevisiae (Sc)4105 ~ ~.
: Trichoderma viride (Tv) 8678 .
- 30 Aureobasidium pullulan (Ap)1~622 Fusarium oxysporum (Fo) 481~2 -:: In Tables lll and IV, the MIC values of the compounds described in Table I as : .
, ~ .. .
; ~;.compared to the MIC of a standard commercial preservative (with 1-(3-chloroallyl)-3,5,7-triaza- .
1-azoniaadamantane chloride as the active agent and referred to herein as ~STANDARD 1 ") are setforthforthebacteriaorganismsandyeasVfungiorganismswhicharelistedinTablell.

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TABLE IV
Minimum Inhibitory Concentrations for Test Compounds in Yeast/Fungi Species (in ppm) .. ~ . . __ ORGANISMS
COMPOU ND
An ¦ Ca PcSc Tv Ap Fo I _ STANDARD I >500 ¦ >500>500 500 >500 >500 >500 A 2.5 ¦ 2.5 2.5 2.5 10 2.5 2.5 B 25 ¦ 25 10 25 50 5 25 l , C 25 1 <10 1 <10 <10 250 <10 25 ¦ 50 50 ¦ 25 ¦100 25 50 E < 10 j < 10 < 10 10 100 < 10 50 F <10 1 <10 <10 <10 25 <10 <10 H 25 25 < 10 c 10 100 < 10 50 10 < 10 < 10 < 10 25 < 10 < 10 J 25 25 25 < 10 100 _ 25 . ..
<10 25 <10 25 -L 2.5 10 Z.S S ~0 S ` ~0 M 2.5 2.5 2.5 2.5 10 2.5 5 N 500> 500 500 > 500 > 500 500 > 500 . _ 500>500 500 >500 >500 500 >500 500>500 500 ~500 >500 500 >500 Q 500 500 500 500 >500 50 >500 100> 500 50 500 > 500 500 > 500 S 100 500 100 500 >500 100 500 ~; 30 T 250>500 250 >500 >500 250 >500 U >500>500 >500 >500 >500 >500 W >500>500 >500 >500 >500 500 >500 WO 93/13106 PCr/US92/10476 21018~ `
Marine Antifoulina Activitv The present invention is also directed to a method for inhibiting marine organisms. The term n marine organisms" is meant to include marine animals, such as barnacles, serpulid, bryozoa, oysters and hydroids, and marine plants, such as green algae and 5 brown algae. The method for inhibiting marine organisms comprises contacting a surface exposedtoamarineenvironmentinwhichmarineorganismsgrowwithamarineantifouling effective amount of the compound of this invention.
As appreciated in the art, not all of the compounds disclosed herein are active at the same concentrations or against the same marine organism species. That is, there is some 10 compound-t~compound variation in marine antifouling potency and spectrum of marine antifouling activity. Furthermore, a compound's marine antifouling activity may be dependent onthespecificmaterialswithwhichthecompoundisformulatedtoformamarineantifouling composition.
As used herein, the term " mari ne antifoul ing effective amount " refers to that lS amountofoneoramixtureoftwoormoreofthecompoundsofthisinventionneededto exhibit inhibition of selected mari ne organisms. Typical Iy, this amount varies from providi ng 1 weight percent to 30 weight percent of the compound to a marine antifouling composition which is used to treat a surface exposed to a marine environment in which marine organisms live or grow. Such amounts vary depending upon the particular compound tested and marine 20 organism tobetreated. Also, the exactconcentration of the compoundsto be added in the preparation of industrial and consumer formulatiorls may vary within a product type depending upon the components of the formulation.
A composition comprising a marine antifouling effective amount of the compound will also typically comprise an inert diluent which may be, for example, in the form 25 of a paint. Particularly preferred are those paints having a vinyl resin binder such as, for example, a plastici~ed polyvinyl chloride or a polyvinyl chloride-polyvinyl acetate type.
Preferably, the binders are formulated as latexes or emulsions. In a paint composition, the com'pound of the present invention is pieferably used in an amount from 1 to 30 weight -~
peKentand,mostpreferably,from 10to25weightpercent. Inadditiontovinylresinbinder 30 paints, epoxy and polyurethane binder paints containing the compound may also be useful .
Coatings and films prepared from paints comprising the compound of the present invention typically remain substantially free from build-up of marine organisms for periods ranging from 3 to 12 months, depending upon the concentration of the compound and the thickness of the applied coating or film.
The term ~ a surface exposed to a marine environment in which marine organisms grow'' refersto a surface where a marine organism naturally or normally lives or grows Typically,suchansurfacewillbeanareathatisincontinualorperiodiccontactwithamarine . ' ,:
.

WO 93/13106 PCl'/US92/10476 21~18g~
environment such as an ocean or other body of water. Typical surfaces include, for example, a ship hull.
The marine antifouling anivity of the compounds of the present invention is demonstrated by the following techniques.
Test panels are prepared from clear, rigid polyvinyl chloride film that is 0 381 x 10-3 m thick and has one textured surface. The test panels are 0.1524 m by 0.1524 m squares that have 0.00635 m holes punched at corners on 0.127 m centers. A 0.102 square template, with a 0.067 m diameter hole at the center, is attached to the center of the textured surface of the test panels.
1~ Acandidatemarineantifoulantcompound(1.0g) isstirred intoa resinouslatex binder (9 0 9~. A portion of the compound/binder mixture ( l .S g) is added to the center of the test panel and uniformly spread over the circular area inside the template.
Water is added dropwise as needed to properly spread the compound/binder mixture. The template preventsthe compound/binder mixture from spreading beyond the uncoveredarea. Thetestpanelisallowedtositforbetweententothirtyminutesuntilthe edge of the spread compound/binder mixture has dried. The template is then removed. The :
test panel is then allowed to dry for 8 to 12 hours at room temperature.
Two test panels are prepared for each candidate marine antifoulant compound.
Two control tfft panels are also prepared by only treating with the resinous latex binder. One 20 test panel of each candidate marine surfactant compound is attached over a white background - to the topside of an exposure support apparatus. The second test panel is attached over a black background tothe underside of the exposure support apparatus. The exposure support .
apparatus is placed horizontally 0.0254 m under a marine surface with the white background topside facing up. The exposure support apparatus is exposed to the marine environment for 25 both 3 and 6 weeks during which time the control test panels become substantially covered with mature marine organism growth on both the topside and underside exposures.
After being removed from the exposure support apparatus, each test panel is inspected and rated for marine organism growth on both the treated and untreated areas of the test panel. The marine organisms present on the treated and untreated areas are noted.
30 The presence of algea spores and bacterial slime are noted but not included in rating each test , panel The test panels are rated on a scale from 10 (representing completely free of marine organism growth) to 0 (representing completely covered with marine organism growth).
In Table V, the marine antifouling rating values for some of the compounds listed j : -InTablelaresetforth,aswellastheratingsforcontrolpanels(usingnoantifouling ; 35 compound) and panels using a standard commercial marine antifouling compound (with : 5-chloro-2- methyl-4-isothiazoli n-3-one and 2-methyl-4-isothiazoli n-3-one as the acti ve agents ~ ~ and eferred to herein as "STANDARD lln).
:

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WO 93/131~ PCr/US92/10476 21 ~.8~
TABLE V
Marine Antifouling Rating for Test Compounds Marine Antifouling Rating-~
S
Compound 3 Week Te~t 6 Week Te~t Top ¦Bottom -Top ¦Bottom Panel I Panel Panel Panel A -~- r -- 8 3 C O ~ 9 5 O
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Claims

1. A compound corresponding to the formula wherein X represents:

or and R1 and R2 independently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, wherein the alkyl, alkoxy, arylcarbonyl, or alkoxy carbonyl may be with or without halogen substituents, provided that at least one of R1 and R2 is a nitro, cyano, alkoxy, arylcarbonyl, or an alkoxy carbonyl group.

2. The compound of Claim 1 wherein R1 and R2 independently represent hydrogen, halogen, nitro, cyano, an alkyl of 1 to 4 carbon atoms, an alkoxy with an alkyl group of 1 to 3 carbon atoms, or an alkoxy carbonyl group with an alkyl group of 1 to 3 carbon atoms.

3 The compound of Claim 1 wherein R1 represents CN, CO7CH3, OCH3, COC6H5 or NO2 when R2 represents H.

4 The compound of Claim 1 wherein R' represents H, Cl, CH3 or NO2 when R2 representS NO2

5. An antimicrobial composition comprising an inert diluent and an antimicrobially-effective amount of a compound corresponding to the formula:

wherein X represents:

or and R1 and R2 independently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, wherein the alkyl, alkoxy, arylcarbonyl, or alkoxy carbonyl may be with or without halogen substituents, provided that at least one of R1 and R2 is a nitro, cyano, alkoxy, arylcarbonyl, or an alkoxy carbonyl group.

6. The composition of Claim 5 wherein R1 and R2 independently represent hydrogen, halogen, nitro, cyano, an alkyl of 1 to 4 carbon atoms, an alkoxy with an alkyl group of 1 to 3 carbon atoms, or an alkoxy carbonyl group with an alkyl group of 1 to 3 carbon atoms.

7. The composition of Claim 5 wherein R1 represents CN, CO2CH3, OCH3, COC6H5 or NO2 when R2 represents H.

8. The composition of Claim 5 wherein R1 represents H, Cl, CH3 or NO2 when R2 represents NO2.

9. The composition of Claim 5 wherein the compound is present in the composition in an amount to provide from 1 part per million to 5,000 parts per million by weight of the compound to an antimicrobial habitat that is contacted with the composition.

10. A method for inhibiting microorganisms in a microbial habitat composing contacting said microbial habitat with an antimicrobially-effective amount of a compound corresponding to the formula:

wherein X represents:

or and R1 and R2 independently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, wherein the alkyl, alkoxy, arylcarbonyl, or alkoxy carbonyl may be with or without halogen substituents, provided that at least one of R1 and R2 is a nitro, cyano, alkoxy, arylcarbonyl, or an alkoxy carbonyl group.

11 The method of Claim 10 wherein R1 and R2 independently represent hydrogen, halogen, nitro, cyano, an alkyl of 1 to 4 carbon atoms, an alkoxy with an alkyl group of 1 to 3 carbon atoms, or an alkoxy carbonyl group with an alkyl group of 1 to 3 carbon atoms.

12. The method of Claim 10 wherein R1 represents CN, CO2CH3, OCH3, COC6H5 or NO2 when R2 represents H.

13. The method of Claim 10 wherein R1 represents H, Cl, CH3 or NO2 when R2 represents NO2.

14. The method of Claim 10 wherein the compound is used in an amount to provide from 1 part per million to 5,000 parts per million by weight of the compound to a microbial habitat being contacted with the composition.

15. The use of a compound corresponding to the formula:

wherein X represents or and R1 and R2 independently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, wherein the alkyl, alkoxy, arylcarbonyl, or alkoxy carbonyl may be with or without halogen substituents, provided that at least one of R1 and R2 is a nitro, cyano, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, as a microorganism inhibitor.

16. The use of Claim 15 wherein R1 and R2 independently represent hydrogen, halogen, nitro, cyano, an alkyl of 1 to 4 carbon atoms, an alkoxy with an alkyl group of 1 to 3 carbon atoms, or an alkoxy carbonyl group with an alkyl group of 1 to 3 carbon atoms.

17. The use of Claim 15 wherein R1 represents CN, CO2CH3, OCH3, COC6H5 or NO2 when R2 represents H.

18. The use of Claim 15 wherein R1 represents H, Cl, CH3 or NO2 when R2 representS NO2-

19. The use of Claim 15 wherein the compound is used in an amount to provide from 1 part per million to 5,000 parts per million by weight of the compound to a microbial habitat being contacted with the composition.

20. A composition useful in preventing the growth of marine organisms on a surface exposed to a marine environment in which marine organisms grow comprising an inert diluent and a marine antifouling effective amount of a compound corresponding to the formula:

wherein X represents:

or and R1 and R2 independently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, wherein the alkyl, alkoxy, arylcarbonyl, or alkoxy carbonyl may be with or without halogen substituents, provided that at least one of R1 and R2 is a nitro, cyano, alkoxy, alkylcarbonyl, or an alkoxy carbonyl group.

21. The composition of Claim 16 wherein R1 and R2 independently represent hydrogen, halogen, nitro, cyano, an alkyl of 1 to 4 carbon atoms, an alkoxy with an alkyl group of 1 to 3 carbon atoms, or an alkoxy carbonyl group with an alkyl group of 1 to 3 carbon atoms.

22. The composition of Claim 16 wherein R1 represents F, Cl, CH3, CF3, CN, CO2CH3, OCH3, COC6H5 or NO2 when R2 represents H.

23. The composition of Claim 16 wherein R1 represents H, Cl, CH3 or NO2 when R2 represents NO2.

24. The composition of Claim 16 wherein the compound is present in the composition in an amount from 1 weight percent to 30 weight percent.

25. A method for preventing the growth of marine organisms on a surface exposed to a marine environment in which marine organisms grow comprising contacting said surface with a marine antifouling effective amount of a compound corresponding to the formula:

wherein X represents:

or and R1 and R2 independently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, wherein the alkyl, alkoxy, arylcarbonyl, or alkoxy carbonyl may be with or without halogen substituents.

26. The method of Claim 25 wherein R1 and R2 independently represent hydrogen, halogen, nitro, cyano, an alkyl of 1 to 4 carbon atoms, an alkoxy with an alkyl group of 1 to 3 carbon atoms, or an alkoxy carbonyl group with an alkyl group of 1 to 3 carbon atoms.

27. The method of Claim 25 wherein R1 represents F, Cl, CH3, CF3, CN, CO2CH3, OCH3, or NO2 when R2 represents H.

28. The method of Claim 25 wherein R1 represents H, Cl, CH3 or NO2 when R2 represents NO2

29. The method of Claim 25 wherein the compound is contacted with the surface in an amount from 1 weight percent to 30 weight percent of a composition comprising an inert diluent and the compound.

30. The use of a compound corresponding to the formula:

wherein X represents:

or and R1 and R2 independently represent hydrogen, halogen, nitro, cyano, alkyl, alkoxy, arylcarbonyl, or an alkoxy carbonyl group, wherein the alkyl, alkoxy, arylcarbonyl, or alkoxy carbonyl may be with or without halogen substituents as a marine organism inhibitor.

31. The use of Claim 30 wherein R1 and R2 independently represent hydrogen, halogen, nitro, cyano, an alkyl of 1 to 4 carbon atoms, an alkoxy with an alkyl group of 1 to 3 carbon atoms, or an alkoxy carbonyl group with an alkyl group of 1 to 3 carbon atoms.

32. The use of Claim 30 wherein R1 represents F, Cl, CH3, CF3, CN, CO2CH3, OCH3, or NO2 when R2 represents H.

33. The use of Claim 30 wherein R1 represents H, Cl, CH3 or NO2 when R2 represents NO2.